Safety Study of Recombinant M2e Influenza-A Vaccine in Healthy Adults (FLU-A)

Tracking Information
First Submitted Date ICMJE	October 10, 2008
First Posted Date ICMJE	January 8, 2009
Results First Submitted Date	November 1, 2011
Results First Posted Date	January 16, 2012
Last Update Posted Date	January 19, 2012
Study Start Date ICMJE	July 2007
Actual Primary Completion Date	January 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 12, 2011)	Number of Participants Reporting Adverse Events by System Organ Class After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or a Placebo Vaccine. [ Time Frame: Day 0 through Day 60 post-vaccination ]; Number of Participants Reporting a Solicited Injection Site or Systemic Adverse Event After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 through Day 7 post-vaccination ]Solicited Injection Site Adverse Events: Erythema, Induration, Pain, Pruritus, Swelling, Rash. Solicited Systemic Adverse Events: Lymph Node Pain, Pyrexia (Temperature), Chills, Constipation, Diarrhoea, Fatigue, Headache, Malaise, Myalgia, Nausea, Vomiting, Alanine Aminotransferase Increased, Aspartate Aminotransferase Increased, Blood Creatinine Increased, Haemoglobin Decreased, Platelet Count Decreased, White Blood Cell Count Increased.; Number of Participants With Evaluated Laboratory Abnormalities After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 through Day 60 post-vaccination 1 ]; Number of Participants With Seroconversion to M2e Antigen During Initial Treatment and Follow Up Period After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine [ Time Frame: Day 15 through Month 10 Post-vaccination 1 ]Seroconversion was defined as an end point anti M2e antibody titer ≥ 100. Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA); Geometric Mean Titers (GMTs) of Vaccine Antibodies After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or a Placebo Vaccine. [ Time Frame: Day 15 through Month 10 Post-vaccination 1 ]Antibody responses to the respective vaccines were assessed by means of enzyme linked immunosorbent assay (ELISA). A GMT value of 50.0 indicates a titer at or below the lowest limit of quantitation (LLOQ)
Original Primary Outcome Measures ICMJE; (submitted: January 6, 2009)	Safety and reactogenicity of ACAM-FLU-A with and without adjuvant compared to placebo control in healthy adult subjects. [ Time Frame: one and one half years ]
Change History	Complete list of historical versions of study NCT00819013 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 12, 2011)	Number of Participants With Signs and Symptoms of Influenza After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Month 4 through Month 10 post-vaccination 1 ]Participants who reported signs and symptoms of influenza were tested using nasal pharyngeal swabs, with secretions cultured using susceptible tissue culture cell lines. Positive cultures were confirmed as influenza using immunofluorescence techniques with influenza strain specific antibodies.; Number of Participants With Seroconversion to M2e Antigen by Immunoglobulin G (IgG) Subclasses Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 and Day 60 Post-vaccination 1 ]Seroconversion was defined as an antibody Titer ≥ 100. Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA); Geometric Mean Titers of Anti-M2e Antigen by Immunoglobulin G (IgG) Subclasses Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 and Day 60 Post-vaccination 1 ]Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA). A GMT value of 50.0 indicates a titer at or below the lowest limit of quantitation (LLOQ).; Geometric Mean Titer Ratios of Anti-M2e Antigen by Immunoglobulin G (IgG) Subclasses Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 and Day 60 Post-vaccination 1 ]Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA).; Geometric Mean Titers (GMTs) of Anti-Hepatitis B Core Antibodies Using Immunoglobulin G (IgG) ELISA Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 and Day 15 through Month 10 post-vaccination 1 ]Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA); Number of Participants With Seropositivity to Hepatitis B Core Antigen Pre- and Post-Vaccination 1 With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. [ Time Frame: Day 0 and Day 15 through Month 10 Post-vaccination 1 ]Seropositivity with ELISA was defined as a Pre- or post-vaccination antibody titer ≥ 100. Seropositivity with the Commercial Kit method was defined as a positive pre- or post-vaccination response. Seropositivity were assessed by means of enzyme linked immunosorbent assay (ELISA) and the Commercial Kit methods
Original Secondary Outcome Measures ICMJE; (submitted: January 6, 2009)	Immunogenicity profile following two doses of ACAM-FLU-A with and without adjuvant compared to placebo control. [ Time Frame: one and one half years ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety Study of Recombinant M2e Influenza-A Vaccine in Healthy Adults
Official Title ICMJE	A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Safety, Reactogenicity, and Immunogenicity of Recombinant M2e Influenza-A Vaccine Candidate ACAM FLU-A) in Healthy Adults
Brief Summary	This multi-center study will be conducted in the United States with up to 80 healthy adult subjects. Subjects will be scheduled to receive a total of two (2) injections with 1 injection each administered. Subjects will be randomized according to a randomization scheme.
Detailed Description	All subjects will be followed up for 60 days post-randomization and through the influenza season. Following the influenza season, a subset of the subjects will receive a booster vaccine at the 12 month time point. The subjects will further be assessed at 2 days, 7 days, 15 days, 30 days and 6 months following the booster vaccination.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
Condition ICMJE	Influenza
Intervention ICMJE	Biological: Influenza A Vaccine: ACAM FLU-A 0.5 mL ACAM-FLU-A low dose + Adjuvant 1, Intramuscular Other Name: ACAM FLU-A; Biological: Influenza A Vaccine: ACAM FLU-A 0.5 mL ACAM-FLU-A low dose + Adjuvant 2, Intramuscular Other Name: ACAM FLU-A; Biological: Influenza A Vaccine: ACAM FLU-A 0.5 mL ACAM FLU-A low dose, Intramuscular Other Name: ACAM FLU-A; Biological: Saline placebo 0.5 mL, Intramuscular Other Name: USP Saline
Study Arms	Experimental: Study Group 1 ACAM-FLU-A low dose + Adjuvant 1 Intervention: Biological: Influenza A Vaccine: ACAM FLU-A; Experimental: Study Group 2 ACAM-FLU-A low dose + Adjuvant 2 Intervention: Biological: Influenza A Vaccine: ACAM FLU-A; Experimental: Study Group 3 ACAM-FLU-A low dose Intervention: Biological: Influenza A Vaccine: ACAM FLU-A; Placebo Comparator: Study Group 4 Saline placebo Intervention: Biological: Saline placebo
Publications *	Ibañez LI, Roose K, De Filette M, Schotsaert M, De Sloovere J, Roels S, Pollard C, Schepens B, Grooten J, Fiers W, Saelens X. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A. PLoS One. 2013;8(3):e59081. doi: 10.1371/journal.pone.0059081. Epub 2013 Mar 18.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 12, 2011)	87
Original Actual Enrollment ICMJE; (submitted: January 6, 2009)	80
Actual Study Completion Date	February 2009
Actual Primary Completion Date	January 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Adult males or females 18 - 40 years of age in good general health Exclusion Criteria: Known allergies or severe reactions to any of the vaccine components including those to adjuvants; History of severe allergic reactions, including angioedema;; History of asthma or recurrent wheezing; (current or within past 2 years);; History of neurological symptoms or signs following administration of any vaccine;
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 40 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00819013
Other Study ID Numbers ICMJE	H-261-001
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sanofi
Study Sponsor ICMJE	Sanofi
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Medical Director Sanofi Pasteur Inc
PRS Account	Sanofi
Verification Date	January 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP